This is an unofficial archive of PsychonautWiki as of 2025-08-11T15:14:44Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.
m I added blackout because it can cause blackouts at high doses (can also speak from experience)
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{{DepressantOD|benzodiazepines}}
{{SummarySheet}}
{{SubstanceBox/Lorazepam}}
{{SubstanceBox/Lorazepam}}
'''Lorazepam''' (trade name '''Ativan''') is a intermediate-duration [[psychoactive]] drug of the [[benzodiazepine]] class which produces anxiolytic, sedative, hypnotic, muscle relaxant, anticonvulsant, anti-nausea and amnestic effects. Lorazepam, like other [[benzodiazepines]], binds to specific sites on the GABAA [[gamma-amino-butyric acid]] receptor. Lorazepam is used for the short-term treatment of [[Effect:Anxiety|anxiety]], insomnia, acute seizures, and sedation of hospitalized patients.<ref>Benzodiazepines and their effects | http://www.benzo.org.uk/hindmarch.htm</ref><ref>An Economic Evaluation of Propofol and Lorazepam for Critically Ill Patients Undergoing Mechanical Ventilation | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763279/</ref><ref>Status epilepticus: an evidence based guide | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226249/</ref><ref>Pharmacological Management of Acute Agitation | http://link.springer.com/article/10.2165%2F00003495-200565090-00003</ref>
'''Lorazepam''' (trade name '''Ativan''' or '''Tavor''') is a [[psychoactive class::depressant]] substance of the [[chemical class::benzodiazepine]] class. Lorazepam is used for the short-term treatment of [[Anxiety|anxiety]], [[insomnia]], [[seizure|acute seizures]], and the sedation of hospitalized patients.<ref>{{Citation | title=benzo.org.uk : Benzodiazepines and their effects, Professor Ian Hindmarch, January, 1997 | url=https://www.benzo.org.uk/hindmarch.htm}}</ref><ref>{{cite journal | vauthors=((Cox, C. E.)), ((Reed, S. D.)), ((Govert, J. A.)), ((Rodgers, J. E.)), ((Campbell-Bright, S.)), ((Kress, J. P.)), ((Carson, S. S.)) | journal=Critical care medicine | title=An Economic Evaluation of Propofol and Lorazepam for Critically Ill Patients Undergoing Mechanical Ventilation | volume=36 | issue=3 | pages=706–714 | date= March 2008 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763279/ | issn=0090-3493 | doi=10.1097/CCM.0B013E3181544248}}</ref><ref>{{cite journal | vauthors=((Walker, M.)) | journal=BMJ : British Medical Journal | title=Status epilepticus: an evidence based guide | volume=331 | issue=7518 | pages=673–677 | date=24 September 2005 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226249/ | issn=0959-8138}}</ref><ref>{{cite journal | vauthors=((Battaglia, J.)) | journal=Drugs | title=Pharmacological Management of Acute Agitation | volume=65 | issue=9 | pages=1207–1222 | date=1 June 2005 | url=https://doi.org/10.2165/00003495-200565090-00003 | issn=1179-1950 | doi=10.2165/00003495-200565090-00003}}</ref>
Users should note that with [[benzodiazepines]], [[Thienodiazepine#Discontinuation|sudden discontinuation]] can be dangerous or even life-threatening for long-term or heavy users. As a result, individuals who are physically dependent on this substance are advised to [[taper]] their dose by gradually lowering the amount taken each day over a prolonged period of time instead of stopping use abruptly.<ref>{{cite journal | vauthors=((Kahan, M.)), ((Wilson, L.)), ((Mailis-Gagnon, A.)), ((Srivastava, A.)) | journal=Canadian Family Physician | title=Canadian guideline for safe and effective use of opioids for chronic noncancer pain. Appendix B-6: Benzodiazepine Tapering | volume=57 | issue=11 | pages=1269–1276 | date= November 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215603/ | issn=0008-350X}}</ref>
==Chemistry==
==Chemistry==
Lorazepam is a drug of the [[benzodiazepine]] class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R<sub>1</sub> and R<sub>4</sub>. Further, the benzodiazepine ring is bonded at R<sub>5</sub> to a 2-chlorinated phenyl ring. R<sub>7</sub> of the benzyl ring is also substituted with a chlorine group. Additionally, Lorazepam contains a hydroxy (OH-) group substituted at R<sub>3</sub>. It also contains an oxygen group double bonded to R<sub>2</sub> of its diazepine ring to form a ketone. This oxygen substitution at R<sub>2</sub> is shared with other benzodiazepine drugs with the suffix -azepam.
==Pharmacology==
==Pharmacology==
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site on the [[GABAA]] [[receptor]] and modulating the function of the [[GABA]] [[receptor]], the most prolific inhibitory receptor within the brain. The GABA chemical and receptor system mediates inhibitory (or calming effects) of alprazolam on the nervous system.
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter [[GABA|gamma aminobutyric acid (GABA)]] by acting on its [[receptor]]s.<ref>{{cite journal | vauthors=((Haefely, W.)) | journal=Neuroscience Letters | title=Benzodiazepine interactions with GABA receptors | volume=47 | issue=3 | pages=201–206 | date=29 June 1984 | issn=0304-3940 | doi=10.1016/0304-3940(84)90514-7}}</ref> As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the [[sedating]] (or [[anxiety suppression|calming effects]]) of lorazepam on the nervous system.
The [[anticonvulsant]] properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.<ref>{{cite journal | vauthors=((McLean, M. J.)), ((Macdonald, R. L.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture | volume=244 | issue=2 | pages=789–795 | date= February 1988 | issn=0022-3565}}</ref>
Lorazepam is thought to have a relatively high affinity for [[GABA]] receptors compared to other benzodiazepines, which may also explain its marked amnesic effects.<ref>{{cite journal | vauthors=((Matthew, E.)), ((Andreason, P.)), ((Pettigrew, K.)), ((Carson, R. E.)), ((Herscovitch, P.)), ((Cohen, R.)), ((King, C.)), ((Johanson, C. E.)), ((Greenblatt, D. J.)), ((Paul, S. M.)) | journal=Proceedings of the National Academy of Sciences of the United States of America | title=Benzodiazepine receptors mediate regional blood flow changes in the living human brain. | volume=92 | issue=7 | pages=2775–2779 | date=28 March 1995 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC42301/ | issn=0027-8424}}</ref>
Relative to other [[benzodiazepines]], lorazepam is thought to have high affinity for [[GABA]] receptors, which may also explain its marked amnesic effects.<ref>Benzodiazepine receptors mediate regional blood flow changes in the living human brain. | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC42301/</ref> The anticonvulsant properties of lorazepam and other benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.<ref>Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. | http://www.ncbi.nlm.nih.gov/pubmed/2450203</ref>
Lorazepam undergoes glucuronidation via Hepatic Pathways which produces lorazepam glucuronide as the main metabolite. The glucuronide attached increases the polarity of the molecule allowing a faster excretion through urine.{{citation needed}}
==Subjective effects==
==Subjective effects==
The effects listed below are based upon the [[subjective effects index]] and personal experiences of [[PsychonautWiki]] [[PsychonautWiki#Contributors|contributors]]. The listed effects will rarely if ever occur all at once but heavier dosages will increase the chances and are more likely to induce a full range of effects.
{{Preamble/SubjectiveEffects}}
===Physical Effects===
{{effects/base
The physical effects of Lorazepam can be broken down into 3 components all of which progressively intensify proportional to dosage. These are described below and generally include:
|{{effects/physical|
*'''[[Effect::Sedation]]'''
*'''[[Effect::Motor control loss]]'''
*'''[[Effect::Muscle relaxation]]
*'''[[Effect::Appetite enhancement]]''' - This effect is not particularly prominent, but is reported to occur in some people. It can have a synergistic effect when combined with [[cannabis]]
*'''[[Effect::Frequent urination]]'''<ref>{{Citation | title=Lorazepam: MedlinePlus Drug Information | url=https://medlineplus.gov/druginfo/meds/a682053.html}}</ref>
*'''[[Physical effects: Sedation|Sedation]]''' - In terms of energy level alterations, Lorazepam is extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
}}
*'''[[Physical effects: Dizziness|Dizzness]]'''
{{effects/paradoxical|
*'''[[Physical effects: Loss of motor control|Loss of motor control]]'''
Paradoxical reactions to [[benzodiazepines]] such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).<ref>{{cite journal | vauthors=((Saïas, T.)), ((Gallarda, T.)) | journal=L’Encephale | title=[Paradoxical aggressive reactions to benzodiazepine use: a review] | volume=34 | issue=4 | pages=330–336 | date= September 2008 | issn=0013-7006 | doi=10.1016/j.encep.2007.05.005}}</ref><ref>{{cite journal | vauthors=((Paton, C.)) | journal=Psychiatric Bulletin | title=Benzodiazepines and disinhibition: a review | volume=26 | issue=12 | pages=460–462 | date= December 2002 | url=https://www.cambridge.org/core/journals/psychiatric-bulletin/article/benzodiazepines-and-disinhibition-a-review/421AF197362B55EDF004700452BF3BC6 | issn=0955-6036 | doi=10.1192/pb.26.12.460}}</ref>
===Cognitive Effects===
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.<ref>{{cite journal | vauthors=((Bond, A. J.)) | journal=CNS Drugs | title=Drug- Induced Behavioural Disinhibition | volume=9 | issue=1 | pages=41–57 | date=1 January 1998 | url=https://doi.org/10.2165/00023210-199809010-00005 | issn=1179-1934 | doi=10.2165/00023210-199809010-00005}}</ref><ref>{{cite journal | vauthors=((Drummer, O. H.)) | journal=Forensic Science Review | title=Benzodiazepines - Effects on Human Performance and Behavior | volume=14 | issue=1–2 | pages=1–14 | date= February 2002 | issn=1042-7201}}</ref>
The cognitive effects of Lorazepam can be broken down into 6 components all of which progressively intensify proportional to dosage. The general head space of Lorazepam is described by many as one of intense sedation and decreased inhibition. It contains a large number of typical [[depressant]] cognitive effects.
}}
|{{effects/cognitive|
The cognitive effects of lorazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of lorazepam is described by many as one of intense sedation and decreased inhibition. In recreational doses it can be very discombobulating. It contains a large number of typical [[depressant]]s cognitive effects. Often compared to [[alprazolam]], lorazepam is noted for having a more sedation and sleepiness but less [[Anxiety reduction|anxiolytic]] effects.
The most prominent of these cognitive effects generally include:
The most prominent of these cognitive effects generally include:
*'''[[Effect::Analysis suppression]]'''
*'''[[Effect::Anxiety suppression]]''' - Not as prominent as with alprazolam, [[clonazepam]] or [[diazepam]].
*'''[[Effect::Appetite enhancement]]'''
*'''[[Effect::Compulsive redosing]]'''
*'''[[Effect::Delusions|Delusions of sobriety]]''' - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages.
*'''[[Effect::Disinhibition]]'''
*'''[[Effect::Dream potentiation]]'''
*'''[[Effect::Emotionality suppression|Emotion suppression]]''' - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of [[antipsychotic]]s. This particular component may even be more prominent on lorazepam than other common benzodiazepines.
*'''[[Effect::Memory suppression]]'''
**'''[[Effect::Amnesia]]'''
*'''[[Effect::Thought deceleration]]''' - This can often be visibly clear to onlookers just during verbal exchanges even on light-medium doses without [[Drug tolerance|tolerance]].
*'''[[Effect::Black out]]'''
}}
}}
===Experience reports===
There are currently no anecdotal reports which describe the effects of this compound within our [[experience index]]. Additional experience reports can be found here:
[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.<ref>{{cite journal | vauthors=((Nutt, D.)), ((King, L. A.)), ((Saulsbury, W.)), ((Blakemore, C.)) | journal=The Lancet | title=Development of a rational scale to assess the harm of drugs of potential misuse | volume=369 | issue=9566 | pages=1047–1053 | date=24 March 2007 | url=https://www.sciencedirect.com/science/article/pii/S0140673607604644 | issn=0140-6736 | doi=10.1016/S0140-6736(07)60464-4}}</ref>]]
Lorazepam likely has a [[Toxicity::low toxicity]] relative to dose.<ref>{{cite journal | vauthors=((Mandrioli, R.)), ((Mercolini, L.)), ((Raggi, M. A.)) | journal=Current Drug Metabolism | title=Benzodiazepine metabolism: an analytical perspective | volume=9 | issue=8 | pages=827–844 | date= October 2008 | issn=1389-2002 | doi=10.2174/138920008786049258}}</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]].
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this substance.
===Tolerance and addiction potential===
Lorazepam is [[Addiction potential::extremely physically and psychologically addictive]].
Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within a couple of days of continuous use]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::7 - 14 days]]. However, in certain cases this may take significantly longer in a manner which is proportional to the duration and intensity of one's long-term usage.
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see [http://www.benzo.org.uk/manual/bzcha02.htm this guide].
[[Benzodiazepine#Discontinuation|Benzodiazepine discontinuation]] is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of [[hypertension]], [[seizures]], and death.<ref>{{cite journal | vauthors=((Lann, M. A.)), ((Molina, D. K.)) | journal=The American Journal of Forensic Medicine and Pathology | title=A fatal case of benzodiazepine withdrawal | volume=30 | issue=2 | pages=177–179 | date= June 2009 | issn=1533-404X | doi=10.1097/PAF.0b013e3181875aa0}}</ref> Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal.
Lorazepam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption all benzodiazepines will have a reduced effect.
===Overdose===
Benzodiazepine overdose may occur when a [[benzodiazepine]] is taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as [[barbiturate |barbiturates]] and [[alcohol]] since they work in a similar fashion, but bind to distinct allosteric sites on the GABA<sub>A</sub> receptor, thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABA<sub>A</sub> receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer<ref>{{cite journal | vauthors=((Twyman, R. E.)), ((Rogers, C. J.)), ((Macdonald, R. L.)) | journal=Annals of Neurology | title=Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital | volume=25 | issue=3 | pages=213–220 | date= March 1989 | issn=0364-5134 | doi=10.1002/ana.410250302}}</ref>. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly.
Symptoms of a benzodiazepine overdose may include severe [[thought deceleration]], [[language suppression |slurred speech]], [[confusion]], [[delusions]], [[respiratory depression]], coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with [[flumazenil]], a GABA<sub>A</sub> antagonist<ref>{{cite journal | vauthors=((Hoffman, E. J.)), ((Warren, E. W.)) | journal=Clinical Pharmacy | title=Flumazenil: a benzodiazepine antagonist | volume=12 | issue=9 | pages=641–656; quiz 699–701 | date= September 1993 | issn=0278-2677}}</ref>, however care is primarily supportive in nature.
*'''[[Cognitive effects: Amnesia|Amnesia]]'''
===Dangerous interactions===
*'''[[Cognitive effects: Suppression of anxiety|Suppression of anxiety]]'''
Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.
*'''[[Cognitive effects: Thought deceleration|Thought deceleration]]'''
*'''[[Cognitive effects: Suppression of information processing|Suppression of information processing]]'''
*'''[[Cognitive effects: Euphoria|Euphoria]]'''
==Toxicity and Harm Potential==
*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2-methyl-2-butanol]], [[alcohol]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]]'') - This combination can result in dangerous or even fatal levels of [[respiratory depression]]. These substances potentiate the [[muscle relaxation]], [[sedation]] and [[amnesia]] caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
===Lethal dosage===
*'''[[Dissociatives]]''' - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
===Tolerance and addition potential===
*'''[[Stimulants]]''' - It is dangerous to combine benzodiazepines with [[stimulant]]s due to the risk of excessive intoxication. Stimulants decrease the [[sedation|sedative]] effect of benzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of benzodiazepines will be significantly increased, leading to intensified [[disinhibition]] as well as [[benzodiazepine#Subjective effects|other effects]]. If combined, one should strictly limit themselves to only dosing a certain amount of benzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
Tolerance to benzodiazepine effects develops with regular use. This is desirable with amnesic and sedative effects, but undesirable with anxiolytic, hypnotic, and anticonvulsant effects. After four to six months of regular benzodiazepine use, evidence of continued efficacy declines. If regular treatment is continued for longer than this, dose increases may be necessary to maintain effects.
[[Benzodiazepine#Discontinuation|Benzodiazepine discontinuation]] is notoriously difficult; it is potentially life threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of seizure following discontinuation of benzodiazepines. Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal.
==Legal status==
Internationally, lorazepam is a Schedule IV drug under the United Nations Convention on Psychotropic Substances.<ref>List of psychotropic substances under international control | http://www.indiapost.gov.in/Pdf/Customs/List_of_Psychotropic_Substances.pdf</ref>
==Legal Issues==
*'''Austria''': Lorazepam is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).{{citation needed}}
'''International:''' The drug is a Schedule IV drug under the United Nations Convention on Psychotropic Substances.[99]
*'''Canada''': Lorazepam is listed in Schedule IV of the Controlled Drugs and Substances Act in Canada.{{citation needed}}
*'''China:''' Lorazepam is a controlled Class II psychotropic substances.<ref>《麻醉药品和精神药品品种目录（2023版）》-国有资产管理处 (tjnu.edu.cn)</ref> Prescriptions for psychotropic substances in Class II are generally limited to a 7-day supply.<ref>卫生部关于印发《麻醉药品、精神药品处方管理规定》的通知 麻醉药品、精神药品处方管理规定__2006年第28号国务院公报_中国政府网 (www.gov.cn)</ref>
*'''Germany''': Lorazepam is controlled under Anlage III BtMG (''Narcotics Act, Schedule III'')<ref name="BtMG_AnlageIII">{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html|title=Anlage III BtMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 26, 2019|language=de}}</ref> as of August 1, 1986.<ref>{{cite web|url=http://www.bgbl.de/xaver/bgbl/start.xav?startbk=Bundesanzeiger_BGBl&jumpTo=bgbl186s1099.pdf|title=Zweite Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften|publisher=Bundesanzeiger Verlag|work=Bundesgesetzblatt Jahrgang 1986 Teil I Nr. 36|publication-date=July 29, 1986|access-date=December 26, 2019|language=de}}</ref> It can only be prescribed on a narcotic prescription form, except preparations which contain up to 2.5 mg lorazepam in each dosage form.<ref name="BtMG_AnlageIII"></ref>
*'''New Zealand''': Lorazepam is a Class C Controlled drug under the Misuse of Drugs Act 1975.<ref>http://legislation.govt.nz/act/public/1975/0116/91.0/DLM436723.html</ref>
*'''Russia''': Lorazepam is a Schedule III controlled substance since 2013.<ref>{{Citation | title=Постановление Правительства РФ от 04.02.2013 N 78 “О внесении изменений в некоторые акты Правительства Российской Федерации” - КонсультантПлюс | url=https://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=141744&dst=100005&date=02.12.2019}}</ref>
*'''Switzerland''': Lorazepam is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''Turkey''': Lorazepam is a 'green prescription' only substance<ref>YEŞİL REÇETEYE TABİ İLAÇLAR | https://www.titck.gov.tr/storage/Archive/2019/contentFile/01.04.2019%20SKRS%20Ye%C5%9Fil%20Re%C3%A7eteli%20%C4%B0la%C3%A7lar%20Aktif%20SON%20-%20G%C3%9CNCEL_58b1ff4a-2e1c-4867-bad7-eec855d6162a.pdf</ref> and illegal when sold or possessed without a prescription.{{citation needed}}
*'''United Kingdom''': Lorazepam is classified as a controlled substance and is listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The Misuse of Drugs Act 1971 makes it illegal to possess it without a prescription and, for such purposes, it is classified as a Class C drug.<ref>{{Citation | title=Drugs licensing | url=https://www.gov.uk/government/collections/drugs-licensing}}</ref>
*'''United States''': Lorazepam is a Schedule IV drug under the Controlled Substances Act.<ref>Drug Scheduling, DEA | https://www.dea.gov/drug-information/drug-scheduling</ref>
*'''Poland''': Lorazepam is controlled under act of psychotropic substances list IV-P Group of "''low potential for abuse''" (with other benzodiazepines in this group). It's legal for medical, scientific and manufacturing purposes. <ref>[https://pl.wikipedia.org/wiki/Wykaz_środków_odurzających_i_substancji_psychotropowych ''Polish wiki about controlled substances (no english translation)'']</ref>
'''United States:''' Lorazepam is a Schedule IV drug under the Controlled Substances Act in the U.S.
==See also==
'''Canada:''' It is a Schedule IV drug under the Controlled Drugs and Substances Act in Canada.
*[[Responsible use]]
*[[Psychoactive substance index]]
*[[Etizolam]]
*[[Benzodiazepines]]
*[[Depressants]]
*[[Volumetric liquid dosing]]
'''United Kingdom:''' It is a Class C, Schedule 4 Controlled Drug under the Misuse of Drugs Regulations 2001.[100]
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Users should note that with benzodiazepines, sudden discontinuation can be dangerous or even life-threatening for long-term or heavy users. As a result, individuals who are physically dependent on this substance are advised to taper their dose by gradually lowering the amount taken each day over a prolonged period of time instead of stopping use abruptly.[6]
Lorazepam is a drug of the benzodiazepine class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R1 and R4. Further, the benzodiazepine ring is bonded at R5 to a 2-chlorinated phenyl ring. R7 of the benzyl ring is also substituted with a chlorine group. Additionally, Lorazepam contains a hydroxy (OH-) group substituted at R3. It also contains an oxygen group double bonded to R2 of its diazepine ring to form a ketone. This oxygen substitution at R2 is shared with other benzodiazepine drugs with the suffix -azepam.
Pharmacology
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter gamma aminobutyric acid (GABA) by acting on its receptors.[7] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of lorazepam on the nervous system.
The anticonvulsant properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.[8]
Lorazepam is thought to have a relatively high affinity for GABA receptors compared to other benzodiazepines, which may also explain its marked amnesic effects.[9]
Lorazepam undergoes glucuronidation via Hepatic Pathways which produces lorazepam glucuronide as the main metabolite. The glucuronide attached increases the polarity of the molecule allowing a faster excretion through urine.[citation needed]
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Appetite enhancement - This effect is not particularly prominent, but is reported to occur in some people. It can have a synergistic effect when combined with cannabis
Paradoxical reactions to benzodiazepines such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).[12][13]
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.[14][15]
Cognitive effects
The cognitive effects of lorazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of lorazepam is described by many as one of intense sedation and decreased inhibition. In recreational doses it can be very discombobulating. It contains a large number of typical depressants cognitive effects. Often compared to alprazolam, lorazepam is noted for having a more sedation and sleepiness but less anxiolytic effects.
The most prominent of these cognitive effects generally include:
Delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages.
Emotion suppression - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of antipsychotics. This particular component may even be more prominent on lorazepam than other common benzodiazepines.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[16]
Lorazepam likely has a low toxicity relative to dose.[17] However, it is [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].
Lorazepam is extremely physically and psychologically addictive.
Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use. After cessation, the tolerance returns to baseline in 7 - 14 days. However, in certain cases this may take significantly longer in a manner which is proportional to the duration and intensity of one's long-term usage.
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see this guide.
Benzodiazepine discontinuation is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of hypertension, seizures, and death.[18] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.
Lorazepam presents cross-tolerance with [[Cross-tolerance::all benzodiazepines]], meaning that after its consumption all benzodiazepines will have a reduced effect.
Overdose
Benzodiazepine overdose may occur when a benzodiazepine is taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as barbiturates and alcohol since they work in a similar fashion, but bind to distinct allosteric sites on the GABAA receptor, thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABAA receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer[19]. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly.
Symptoms of a benzodiazepine overdose may include severe thought deceleration, slurred speech, confusion, delusions, respiratory depression, coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with flumazenil, a GABAA antagonist[20], however care is primarily supportive in nature.
Dangerous interactions
Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
Stimulants - It is dangerous to combine benzodiazepines with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of benzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of benzodiazepines will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of benzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
Legal status
Internationally, lorazepam is a Schedule IV drug under the United Nations Convention on Psychotropic Substances.[21]
Austria: Lorazepam is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).[citation needed]
Canada: Lorazepam is listed in Schedule IV of the Controlled Drugs and Substances Act in Canada.[citation needed]
China: Lorazepam is a controlled Class II psychotropic substances.[22] Prescriptions for psychotropic substances in Class II are generally limited to a 7-day supply.[23]
Germany: Lorazepam is controlled under Anlage III BtMG (Narcotics Act, Schedule III)[24] as of August 1, 1986.[25] It can only be prescribed on a narcotic prescription form, except preparations which contain up to 2.5 mg lorazepam in each dosage form.[24]
New Zealand: Lorazepam is a Class C Controlled drug under the Misuse of Drugs Act 1975.[26]
Russia: Lorazepam is a Schedule III controlled substance since 2013.[27]
Switzerland: Lorazepam is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.[28]
Turkey: Lorazepam is a 'green prescription' only substance[29] and illegal when sold or possessed without a prescription.[citation needed]
United Kingdom: Lorazepam is classified as a controlled substance and is listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The Misuse of Drugs Act 1971 makes it illegal to possess it without a prescription and, for such purposes, it is classified as a Class C drug.[30]
United States: Lorazepam is a Schedule IV drug under the Controlled Substances Act.[31]
Poland: Lorazepam is controlled under act of psychotropic substances list IV-P Group of "low potential for abuse" (with other benzodiazepines in this group). It's legal for medical, scientific and manufacturing purposes. [32]
↑McLean, M. J., Macdonald, R. L. (February 1988). "Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture". The Journal of Pharmacology and Experimental Therapeutics. 244 (2): 789–795. ISSN0022-3565.
↑Drummer, O. H. (February 2002). "Benzodiazepines - Effects on Human Performance and Behavior". Forensic Science Review. 14 (1–2): 1–14. ISSN1042-7201.
↑Mandrioli, R., Mercolini, L., Raggi, M. A. (October 2008). "Benzodiazepine metabolism: an analytical perspective". Current Drug Metabolism. 9 (8): 827–844. doi:10.2174/138920008786049258. ISSN1389-2002.
↑Lann, M. A., Molina, D. K. (June 2009). "A fatal case of benzodiazepine withdrawal". The American Journal of Forensic Medicine and Pathology. 30 (2): 177–179. doi:10.1097/PAF.0b013e3181875aa0. ISSN1533-404X.
↑Twyman, R. E., Rogers, C. J., Macdonald, R. L. (March 1989). "Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital". Annals of Neurology. 25 (3): 213–220. doi:10.1002/ana.410250302. ISSN0364-5134.
↑Hoffman, E. J., Warren, E. W. (September 1993). "Flumazenil: a benzodiazepine antagonist". Clinical Pharmacy. 12 (9): 641–656; quiz 699–701. ISSN0278-2677.
